Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin Q. GU*, H. H.-X. XIA*, W. H. WANG*,  , J. D. WANG*, W. M. WONG*, A. O. O. CHAN*, M. F. YUEN*, S. K. LAM*, H. K.-L. CHEUNG*, X. G. LIU  & B. C.-Y. WONG* *Department of Medicine, University of Hong Kong, Hong Kong;  Department of Gastroenterology, First Hospital, Peking University, Beijing, China Accepted for publication 12 July 2004 SUMMARY Background: We previously reported that aspirin inhib- ited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole. Aim: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori. Methods: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometa- cin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively. Results: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respect- ively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P ¼ 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the num- ber of CFU/mL by 1 log at 24 h compared with that at 0 h (P ¼ 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P ¼ 0.016), and 0.3 mm indometacin at 48 h (P ¼ 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001). Conclusion: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose- dependent manner, and increased its susceptibility to the antibiotics. INTRODUCTION Cyclo-oxygenase (COX), the key enzyme for synthesis of mucosal protective prostaglandins (PG), exists in two isoforms (COX-1 and COX-2). COX-1 is constitu- tively expressed in the gastrointestinal tract in large quantities and COX-2 is induced predominantly during inflammation. The selective and non-selective COX inhibitors belong to non-steroidal anti-inflamma- tory drugs (NSAID). NSAID and Helicobacter pylori infection are two major independent factors causing gastric injuries such as gastric erosion and peptic ulcers. However, their interactions remain unclear. In particular, NSAID and H. pylori have opposite effects on COX and PG synthesis; NSAID decrease COX expression and PG synthesis whereas H. pylori increases COX-2 expression, and PG synthesis in the gastric mucosa, 1–3 indicating that H. pylori infection Correspondence to: Dr B. C. Y. Wong, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. E-mail: bcywong@hku.hk Aliment Pharmacol Ther 2004; 20: 675–681. doi: 10.1111/j.1365-2036.2004.02168.x Ó 2004 Blackwell Publishing Ltd 675